For mammals (specifically domestic animals and pet animals) including human beings, birds (specifically domestic chickens and pet birds), amphibians, reptiles, fish (specifically pet fish) and invertebrates and plants, it is a pressing issue to establish methods for preventing or treating diseases including infection protection techniques. In addition, to accomplish this, methods are strongly required in which no chemical is used, no environmental pollution occurs, no resistant bacteria occurs and no accumulation occurs in human bodies. The present inventors have already discovered for the above problem that an immunopotentiator derived from a natural product safely accomplishes effects for the prevention and treatment of diseases (Non-patent Literature 1). As one example thereof, lipopolysaccharide obtained from Pantoea agglomerans which is resident bacteria in wheat can be used (Non-patent Literature 1). It is known that Limulus-positive glycolipid has a strong immunoenhancement activity (Non-patent Literature 2). The so-called lipopolysaccharide is also included in this category. The lipopolysaccharide is known to be a major component of a cell outer wall of gram-negative bacteria as well as one of the major ingredients of Coley's vaccination and has a potent immunopotentiation activity (Non-patent Literature 3).
The present inventors have discovered that the Limulus-positive glycolipids are present in wheat, a part thereof is the lipopolysaccharide of wheat-symbiotic bacteria and these strongly activate a natural immunity (Non-patent Literature 4). The above two safely and strongly activate the natural immunity by percutaneous or oral administration, and exhibit the effects for the prevention and treatment of a wide range of diseases including infectious diseases (Non-patent Literature 5). Furthermore, the present inventors have reported that not only is a content of the lipopolysaccharide derived from Pantoea agglomerans increased by fermenting wheat flour with Pantoea agglomerans which is resident bacteria in wheat flour, but also that a fermented wheat extract which is a novel immunopotentiator containing components derived from wheat exerts an infection protection effect as a safe and reliable natural material in place of antibiotic chemicals in the fields of stockbreeding and aquaculture.
A basic structure of the lipopolysaccharide is composed of a lipid referred to as lipid A and various sugars (polysaccharide) covalently bound thereto. A region subsequent to the lipid A is composed of R core which takes a relatively uniform structure in related bacteria followed by an O antigen polysaccharide portion which takes a different structure depending on bacterial species (Non-patent Literature 7). The O antigen also has a repeating structure of the same oligosaccharide which characterizes LPS (lipopolysaccharide) (Non-patent Literature 1). Therefore, the lipopolysaccharide generally forms a mixture having multiple molecular weights. It is also known that the lipopolysaccharide has a different structure depending on a microorganism from which the lipopolysaccharide is derived. For example, the lipopolysaccharide derived from Salmonella and the lipopolysaccharide derived from Escherichia coli are different in structure and also biological activity. However, because generally it is not easy to determine the structure of lipopolysaccharide, details of the structures and functions of the lipopolysaccharides derived from the gram-negative bacteria are not known. Thus, it is described that the lipopolysaccharide generally has a novel structure based on functional difference.
Meanwhile, it has been demonstrated in recent studies that the lipopolysaccharide activates the natural immunity via TLR4 (Non-patent Literature 6). It has been found that the lipid A portion of the lipopolysaccharide is essential for binding to TLR4 and that the polysaccharide portion largely affects an efficiency of intracellular signal transduction of TLR4. From the above, it is speculated that the difference in cellular response of the lipopolysaccharide indicates the structural difference.
It is important for establishing the usefulness of the lipopolysaccharide to demonstrate that the percutaneous or oral administration of the lipopolysaccharide is reliable and safe. Thus, gram-negative bacteria used in the production and fermentation of foods conventionally was emphasized. That is, if the Limulus-positive glycolipid and the lipopolysaccharide are present in gram-negative bacteria used in the production of foods and provided as edible products with fermented products, this fact demonstrates that the Limulus-positive glycolipid and the lipopolysaccharide have the experience of being eaten. This is a finding which strongly indicates that the percutaneous or oral administration of the Limulus-positive glycolipid or the lipopolysaccharide is reliable and safe, and simultaneously should make it possible to develop new health care products and pharmaceuticals such as cosmetics and foods using these substances.    [Non-patent Literature 1] Chie Kohchi et al., “Natural immunity regulatory action of fermented wheat extract,” New Food Industry (2006) Vol. 48, p. 19-27    [Non-patent Literature 2] Ulmer, A. J. et al., “Lipopolysaccharide: Structure, Bioactivity, Receptors, and Signal Transduction.” Trends in Glycoscience and Glycotechnology, (2002) Vol. 14, p. 53-68    [Non-patent Literature 3] Stames, C. O., “Coley's toxins in perspective.” Nature, (1992) Vol. 357, p. 11-12    [Non-patent Literature 4]: Nishizawa, T. et al., Chem. Pharm. Bull., (1992), Vol. 40, p. 479-483    [Non-patent Literature 5] Inagawa H. et al., “Effects of lipopolysaccharide (LPSW) derived from wheat flour having macrophage activating effect on treatment and prevention of various diseases,” Biotherapy, (1991) Vol. 5, p. 617-621    [Non-patent Literature 6] Kiyoshi Takedal, et al., “Toll-like receptors in innate immunity.” International Immunology, Vol. 17, p. 1-14    [Non-patent Literature 7] Seikagaku Jiten 2nd edition (1990), Tokyo Kagaku Dojin, p. 1949.